Catabasis, Led by Sirtris Vets, Seeks to Fight Diabetes by Controlling Inflammation

4/21/10Follow @xconomy

One of the big ideas in diabetes research today is that inflammation is one of the major culprits. Tamp down inflammation, and maybe you can reduce the assault on blood vessels that leads to all sorts of complications like heart attacks, blindness, and amputations. If this can be proven over time, Cambridge, MA-based Catabasis Pharmaceuticals might have just the drugs to stop the inflammation and all its nasty effects.

That’s the concept anyway, and it’s one that Catabasis is being richly financed to pursue. The Cambridge, MA-based company has secured a $39.6 million Series A financing from SV Life Sciences, Clarus Ventures, and MedImmune Ventures. We first broke the story last week saying that Catabasis pocketed the first $7.7 million tranche of this deal. CEO Jill Milne confirmed the figure today, adding that Catabasis will get the rest of the money if it can hit certain development goals.

The Catabasis story began in the summer of 2008 when Milne and her colleague Mike Jirousek decided to leave senior jobs at Sirtris Pharmaceuticals after it was acquired by GlaxoSmithKline. They started talking with Steven Shoelson, a leading researcher at Harvard Medical School and the Joslin Diabetes Center, about the emerging understanding of inflammation as an underlying culprit in diabetes. The diabetes market is one of the biggest in the pharmaceutical industry, with an estimated 24 million people in the U.S.—almost one out of every 12 people—suffering from adult-onset or Type 2 diabetes. Incidence has roughly tripled over the past three decades as more people eat unhealthy diets, and live sedentary lives.

The pharmaceutical market has responded to this epidemic by flooding doctors and patients with drugs like metformin, various forms of insulin, GLP-1 inhibitors, and DPP4 inhibitors that work in different ways to keep blood sugar under control. Yet despite all that intense effort at every Big Pharma company, no one has yet gotten a drug approved for Type 2 diabetes that works by controlling inflammation.

“This is a novel way of treating the disease,” Milne says. “It got me excited.”

Catabasis has a plan to tackle this problem with what amounts to a combination drug strategy. Milne and Jirousek, who are trained in biochemistry and chemistry, respectively, started piecing this plan together after they heard about some promising results from Shoelson’s research. His team had shown that a generic anti-inflammatory drug, a type of salicylate, was effective at helping reduce blood sugar in a clinical trial. But there was a catch. The patients had to get a whopping 4 grams a day, and take their pills three times daily. And, researchers saw a case of tinnitus, a serious condition in which people suffer from ringing in their ears, which isn’t an effect the FDA or patients would consider allowable for treating a chronic condition like diabetes.

“That was not acceptable,” Milne says.

While some scientists have pursuing the anti-inflammatory hypothesis, others have been studying Omega-3 fatty acids—those heralded substances in fish oil that are said to be good for you. Those compounds are thought to work by triggering natural anti-inflammatory pathways. But the same dosing problem existed there. So Milne and Jirousek, trained in biochemistry and chemistry, respectively, wondered what would happen in if they could combine salicylate with Omega-3 fatty acids. Could those two types of drugs be combined in a low-dose, convenient, once-daily pill? The drugs ought to be more tolerable together at lower doses, they reasoned.

“We figured if we could bring them together, there would be synergy,” Milne says.

That’s what Catabasis has been doing since the summer of 2008. Milne and Jirousek developed what they call “SMART-linker” technology which attaches the compounds together into a dual-action drug that is considered a new chemical entity. Catabasis didn’t license this technology from anywhere—it was developed in-house over the past 18 months, Milne says. The patent applications have been submitted, and some early animal experiments are in from six different models of inflammation.

The investors have placed their bets that Catabasis can make enough progress to bring its lead drug candidate into its first clinical trials as soon as 2011. And while the company is concentrating on making progress with that lead candidate, Milne also stressed that Catabasis has a platform technology that it wants to further develop as a source of other drugs against inflammation diseases, like inflammatory bowel disease and rheumatoid arthritis.

Catabasis currently has seven employees. With the new financing in hand, it plans to add four or five more people this year with skills in pharmacology, clinical development, and biology, Milne says. Much of their work in the near future will be about showing progress against Type 2 diabetes, but also about showing that these combination anti-inflammatory drugs can be made into safe, once-daily pills that have potential against other diseases that affect millions of people.

“This technology is unique in its ability to treat other diseases,” Milne says. “That’s what got me excited.”

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